Barbara A Hutten

Netherlands Bioinformatics Centre, Nymegen, Gelderland, Netherlands

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Publications (169)1079.87 Total impact

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    ABSTRACT: Venous thromboembolism (VTE), including pulmonary embolism (PE) is often accompanied by stress-hyperglycemia. Vice versa, there is evidence that hyperglycemia contributes to coagulation activation and hypofibrinolysis, resulting in a pro-thrombotic state.
    11/2015; 10(3):145-146. DOI:10.1007/s12467-012-0100-5
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    ABSTRACT: Four-factor prothrombin complex concentrate (PCC) 50 iu/kg is able to swiftly restore haemostatic parameters in healthy subjects on rivaroxaban. We hypothesized that lower dosages of PCC may be sufficient to restore normal haemostasis. In this double-blind, crossover, placebo-controlled study, we compared the effects of PCC 37·5 iu/kg, PCC 25 iu/kg, and placebo on thrombin generation (endogenous thrombin potential, ETP) and prothrombin time in six healthy subjects receiving twice-daily rivaroxaban 15 mg for 2·5 days. Fifteen min after infusion of PCC 37·5 iu/kg, ETP increased from 47 ± 16% to 64 ± 22% (P = 0·03; pre-rivaroxaban ETP: 92 ± 14%) and remained higher than after placebo over 24 h (P = 0·001). PCC 25 iu/kg did not modify ETP within 15 min (53 ± 11% to 59 ± 12%; P = 0·14) and was not different from placebo over 24 h (P = 0·31). ETP reached pre-rivaroxaban levels within 6 h after PCC 37·5 iu/kg infusion and within 12-24 h after PCC 25 iu/kg infusion. Both dosages restored rivaroxaban-induced prothrombin time prolongation after 15 min (P < 0·001). Placebo did not have an effect on coagulation parameters. 37·5 iu/kg of PCC leads to partial restoration of thrombin generation, whereas 25 iu/kg does not. PCC 37·5 iu/kg may be insufficient for immediate full reversal of peak therapeutic rivaroxaban levels.
    British Journal of Haematology 10/2015; DOI:10.1111/bjh.13821 · 4.71 Impact Factor
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    ABSTRACT: Background: Kawasaki disease (KD) is an acute pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. Concerns have been raised regarding the possibility of a predisposition of KD to premature cardiovascular disease (CVD) risk later in life. Our aim was to assess carotid intima-media thickness (cIMT), as a surrogate marker of CVD risk, in patients with a history of KD compared with unaffected controls.Methods and Results:B-mode ultrasound cIMT measurements were performed in 168 patients with a history of KD, and 82 controls; 7 patients were excluded because of incomplete cIMT assessments. Mean cIMT (±SD) was increased in patients with KD compared with controls (0.378±0.030 mm vs. 0.360±0.027 mm, respectively; P adjusted <0.0001). If the cIMTs of CAA-negative patients and controls were plotted against age, increased cIMT was only apparent at young age. In patients with CAA, increased cIMT was observed over the entire age range. Conclusions: Our findings show that arterial wall thickening is more apparent in patients with a history of KD as compared with controls. In CAA-negative patients, cIMT is indistinguishable from controls at older age, whereas an increased cIMT is observed at any age in patients with CAA, suggesting a more general and severe effect of KD on the arterial wall.
    Circulation Journal 10/2015; DOI:10.1253/circj.CJ-15-0555 · 3.94 Impact Factor

  • European Respiratory Journal 09/2015; 13(suppl 59):483-483. DOI:10.1183/13993003.congress-2015.PA4567 · 7.64 Impact Factor
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    Ilse K Luirink · Barbara A Hutten · Albert Wiegman ·
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    ABSTRACT: Cardiovascular disease (CVD) is still the most prominent cause of death and morbidity in the world, and one of the major risk factors for developing CVD is hypercholesterolemia. Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by markedly elevated plasma low-density lipoprotein cholesterol and premature coronary heart disease. Currently, several treatment options are available for children with FH. Lifestyle adjustments are the first step in treatment. If this is not sufficient, statins are the preferred initial pharmacological therapy and they have been proven effective and safe. However, treatment goals are often not achieved and, hence, there is a need for novel treatment options. Currently, several options are being studied in adults and first results are promising. However, studies in children are still to be awaited.
    Current Cardiology Reports 09/2015; 17(9):629. DOI:10.1007/s11886-015-0629-1 · 1.93 Impact Factor
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    ABSTRACT: Fibroblast growth factor 21 (FGF21) has been described to have beneficial effects on glucose and lipid metabolism, and FGF21 analogs are currently evaluated in phase 1 trials. However, the complete spectrum of effects and regulators of FGF21 is yet partly elucidated. Recent studies have shown that FGF21 plays a role in transmembrane cholesterol transport. We set out to examine the association between FGF21 and LDLR mediated transmembrane cholesterol transport, by comparing FGF21 levels in patients with genetically impaired LDLR function and unaffected relatives. Secondly, we explored whether the severity of the LDLR mutation was associated with FGF21 levels. We performed a cross-sectional study in carriers of an LDLR mutation and their unaffected relatives. Subjects were eligible if they participated in the Dutch national screening program for familial hypercholesterolemia (FH), were 18-55 years old, and were carrier of a pathogenic LDLR mutation with an untreated LDL-C level below the 75(th) or above the 90(th) percentile of the general population, or did not carry an FH mutation. The outcome measure was the level of FGF21, which was assessed using ELISA. We included 224 carriers of an LDLR mutation and 148 unaffected relatives. FGF21 levels were lower in LDLR mutation carriers compared to unaffected relatives (median [interquartile range]: 96.92 [60.80-174.05] versus 136.98 [77.34-219.47] pg/mL, respectively; p = 0.08), but after adjusting for potential confounders, there was no association between LDLR mutations and FGF21 levels (p = 0.70). Neither, did we find a relationship between the severity of LDLR mutations and FGF21 levels (p = 0.51, after adjustment for potential confounders). We showed that levels of FGF21 are not different in patients with and without LDLR mutations, which suggests that decreased LDLR expression does not have a negative effect on FGF21 levels. Given the potential beneficial effects of FGF21 analogs on lipids and lipoproteins in a phase 1 study, we deem this of great interest for future treatment options for FH patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 08/2015; 241(2). DOI:10.1016/j.atherosclerosis.2015.05.032 · 3.99 Impact Factor
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    ABSTRACT: BACKGROUND: Four-factor prothrombin complex concentrate (PCC, Cofact, Sanquin Blood Supply) 50 IU/kg increased thrombin generation beyond baseline values in healthy, rivaroxaban-treated subjects. OBJECTIVE: Assess whether infusion with doses of 37.5 and 25 IU/kg of PCC reverses the anticoagulant effect of high dose apixaban, another oral direct factor Xa inhibitor. METHODS: In a randomized, double-blind, placebo-controlled, crossover study, 6 healthy subjects received twice-daily apixaban 10 mg for 3.5 days followed by a single bolus of PCC 37.5 IU/kg, PCC 25 IU/kg, or placebo. The primary outcome was the effect of PCC 15 minutes after infusion on thrombin generation (endogenous thrombin potential [ETP]); secondary outcomes were the immediate effect of PCC on prothrombin time (PT) and the effect of PCC compared with placebo over 24 hours on ETP and PT. RESULTS: Fifteen minutes after infusion of 37.5 IU/kg and 25 IU/kg PCC, ETP increased from 41±11% to 56±23% (p=0.06) and from 44±12% to 51±15% (p=0.03), respectively. ETP significantly differed over time between PCC 37.5 IU/kg and placebo during 24 hours after infusion (p<0.01). Both PCC dosages restored apixaban-induced PT prolongation after 15 minutes (p<0.01) which was sustained over 24 hours. CONCLUSION: Both PCC 37.5 IU/kg and 25 IU/kg improved coagulation parameters in healthy subjects, suggestive of partial reversal of the anticoagulant effect of apixaban. This implies that PCC might be considered in patients with apixaban-associated bleeding. However, ETP was not immediately restored to pre-apixaban levels suggesting that these dosages are too low to instantly and fully restore haemostasis at peak apixaban levels.
    Journal of Thrombosis and Haemostasis 08/2015; DOI:10.1111/jth.13115 · 5.72 Impact Factor
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    Sanne M Dietz · Carline E A Tacke · Barbara A Hutten · Taco W Kuijpers ·
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    ABSTRACT: Kawasaki disease (KD) is a systemic pediatric vasculitis. Its main complication is the development of coronary arterial aneurysms (CAA), causing an increased risk for ischemia and myocardial infarction. It is unclear whether KD patients, apart from the presence of CAA, have an increased cardiovascular disease (CVD) risk due to the previous systemic vasculitis. The aim of this study was to systematically review and meta-analyse the literature regarding surrogate markers for CVD risk in KD patients. Medline and Embase were searched for articles comparing endothelial dysfunction (flow-mediated dilation, nitroglycerin-mediated dilation and peripheral arterial tonometry), vascular stiffness (stiffness index, pulse wave velocity) and carotid intima-media thickness (cIMT) between patients and controls. Two investigators assessed the articles for eligibility and evaluated quality. Thirty studies were included. For all outcomes, moderate to high heterogeneity between studies was found. Most studies reported a decreased flow-mediated dilation in the whole KD- and CAA-positive group compared to controls, while data on CAA-negative patients were conflicting. The stiffness index was increased in the majority of studies evaluating the whole KD- and CAA-positive group, but not in most studies on CAA-negative patients. Mean cIMT was neither significantly increased in the whole KD-group nor in the CAA-positive group nor in most studies studying CAA-negative patients. Studies measuring maximum cIMT were conflicting. Literature suggests that surrogate markers for CVD risk in KD patients are increased in CAA-positive but not in CAA-negative patients. This may indicate that CAA-positive patients should be monitored for CVD in later life. The results of this review have to be interpreted with care due to substantial heterogeneity between studies and methodological limitations, as well as the lack of long-term follow-up studies.
    PLoS ONE 07/2015; 10(7):e0130913. DOI:10.1371/journal.pone.0130913 · 3.23 Impact Factor
  • Saskia Middeldorp · Barbara A Hutten ·
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    ABSTRACT: Clinical question: Is long-term (≥3 months) vs short-term therapy with vitamin K antagonists (VKAs) associated with differences in the incidence of recurrent venous thromboembolism (VTE), major bleeding, and mortality in patients with symptomatic VTE? Bottom line: Long-term treatment with VKAs is associated with a reduced risk for recurrent VTE and an increased risk for major bleeding compared with short-term treatment in patients with VTE, but is not associated with differences in mortality.
    JAMA The Journal of the American Medical Association 07/2015; 314(1):72-73. DOI:10.1001/jama.2015.2693 · 35.29 Impact Factor
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    ABSTRACT: Statins are currently the preferred pharmacological therapy in children with familial hypercholesterolemia (FH) with the aim to prevent premature cardiovascular disease (CVD). However, concerns have been raised that lowering cholesterol levels with statins could interfere with hormone production. In this study hormone concentrations were assessed in young adult FH subjects before and 10 years after the initiation of statins, and compared with their unaffected siblings. All 214 FH children (8-18 years) who were previously randomized into a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, and their 95 unaffected siblings, were eligible. Women using oral contraceptives were excluded. Fasted blood samples were taken to measure lipids and testosterone (males), estradiol (females), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and dehydroepiandosterone (DHEAS). After ten years, gonadal steroid and gonadotropin concentrations were within the reference interval and did not differ between FH subjects (n = 88) and unaffected siblings (n = 62). Mean DHEAS concentrations (±standard deviation) in the FH subjects and female siblings were normally distributed within the reference interval, whereas male siblings had a higher mean DHEAS concentration than their FH brothers (12.9 [± 4.9] vs. 8.4 [± 3.0] μmol/L, respectively, p < 0.0001). After ten years of statin treatment, testosterone, estradiol, LH and FSH concentrations in young adult FH patients are within the reference interval and comparable to their unaffected siblings. These results strengthen current guidelines that statins in FH subjects could be safely used from childhood onwards to prevent premature CVD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 06/2015; 241(2). DOI:10.1016/j.atherosclerosis.2015.05.034 · 3.99 Impact Factor
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    Marjet J A M Braamskamp · Barbara A Hutten · Albert Wiegman ·
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    ABSTRACT: This article provides recent insights on the early onset of atherosclerosis in heterozygous familial hypercholesterolemia and reports on novel treatment options as well as on the consequences of long-term statin use in childhood. Children with familial hypercholesterolemia have greater mean carotid intima-media thickness (cIMT) than their unaffected siblings even before the age of 8 years, which is several years earlier than previously reported. In those children, 2 years of rosuvastatin treatment resulted in slowing of the cIMT progression. In addition, in a 10-year follow-up study after a pravastatin intervention trial, long-term statin therapy in young adult familial hypercholesterolemia patients was associated with normalization of cIMT progression and appeared effective in prevention of very premature cardiovascular events. These effects were observed without untoward safety concerns. However, a majority of these young adults did not reach cholesterol goals according to general guidelines, indicating the need for improvement of treatment in this patient group. The importance, efficacy and safety of early initiation statin therapy in familial hypercholesterolemia children were further confirmed by recent findings. Nevertheless, to reach current treatment goals, the use of more potent statins is required and has been proven well tolerated and effective in young children.
    Current opinion in lipidology 06/2015; 26(3):236-9. DOI:10.1097/MOL.0000000000000177 · 5.66 Impact Factor
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    ABSTRACT: Background: A large number of studies have shown an association between inherited thrombophilia and recurrent miscarriage. It has been hypothesized that anticoagulant therapy might reduce the number of miscarriages and stillbirth in these women. In the absence of randomized controlled trials evaluating the efficacy of anticoagulant therapy in women with inherited thrombophilia and recurrent miscarriage, a randomized trial with adequate power that addresses this question is needed. The objective of the ALIFE2 study is therefore to evaluate the efficacy of low-molecular-weight heparin (LMWH) in women with inherited thrombophilia and recurrent miscarriage, with live birth as the primary outcome. Methods/Design: Randomized study of LMWH plus standard pregnancy surveillance versus standard pregnancy surveillance alone. Discussion: After an initial period of slow recruitment, the recruitment rate for the study has increased. Improved awareness of the study and acknowledgement of the need for evidence are thought to be contributing to the improved recruitment rates. We aim to increase the number of recruiting centers in order to increase enrollment into the ALIFE2 study. Trial registration: The ALIFE2 study was registered on 19 March 2012 under registration number NTR3361.
    Trials 05/2015; 16(1):208. DOI:10.1186/s13063-015-0719-9 · 1.73 Impact Factor
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    ABSTRACT: Intensive glucose control, often involving insulin treatment, failed to improve cardiovascular outcomes in several clinical trials. Observational studies reported an association between insulin use and cardiovascular disease (CVD) risk. It has therefore been suggested that insulin adversely affects CVD risk. To investigate the feasibility of this hypothesis, we studied the association between insulin dose and CVD risk in type 2 diabetes. A case-control study was conducted of new users of oral antidiabetics who were prescribed insulin, using the Dutch Pharmo database. Cases were hospitalized for a cardiovascular event (CVE) and matched 1:2 to patients who were not hospitalized for a CVE, by sex, age, duration of diabetes and type of oral antidiabetic. Patients were divided into tertiles according to mean daily insulin dose. Conditional logistic regression analyses were used to explore the association between insulin exposure and CVE risk. We included 836 patients (517 (62%) male, mean age 66 years). After adjusting for available potential confounders, including HbA1c and triglycerides, insulin exposure was positively related to CVE risk (odds ratios for high (≥53.0 U/day) and intermediate (24.3-52.9 U/day) vs. low exposure (≤24.2 U/day): 3.00 [95% confidence interval (CI) 1.70 to 5.28] and 2.03 [95% CI 1.17 to 3.52]. Our findings are in line with the suggestion that high-dose insulin therapy adversely affects CVD risk, but need to be interpreted with caution due to the observational nature of the study. The role of particularly high-dose insulin in the progression of CVD warrants further investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 03/2015; 240(2):318-323. DOI:10.1016/j.atherosclerosis.2015.03.040 · 3.99 Impact Factor
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    ABSTRACT: Familial hypercholesterolemia is characterized by impaired uptake of cholesterol in peripheral tissues, including the liver and the pancreas. In contrast, statins increase the cellular cholesterol uptake and are associated with increased risk for type 2 diabetes mellitus. We hypothesize that transmembrane cholesterol transport is linked to the development of type 2 diabetes. To assess the association between type 2 diabetes prevalence and familial hypercholesterolemia. Cross-sectional study in all individuals (n = 63 320) who underwent DNA testing for familial hypercholesterolemia in the national Dutch screening program between 1994 and 2014. Deleteriousness and nondeleteriousness of familial hypercholesterolemia mutations were based on literature or laboratory function testing. Low-density lipoprotein (LDL) receptor mutations were considered more severe than apolipoprotein B gene (APOB) mutations, and receptor-negative LDL receptor mutations were considered more severe than receptor-deficient mutations. Prevalence of type 2 diabetes. The prevalence of type 2 diabetes was 1.75% in familial hypercholesterolemia patients (n = 440/25 137) vs 2.93% in unaffected relatives (n = 1119/38 183) (P < .001; odds ratio [OR], 0.62 [95% CI, 0.55-0.69]). The adjusted prevalence of type 2 diabetes in familial hypercholesterolemia, determined using multivariable regression models, was 1.44% (difference, 1.49% [95% CI, 1.24%-1.71%]) (OR, 0.49 [95% CI, 0.41-0.58]; P < .001). The adjusted prevalence of type 2 diabetes by APOB vs LDL receptor gene was 1.91% vs 1.33% (OR, 0.65 [95% CI, 0.48-0.87] vs OR, 0.45 [95% CI, 0.38-0.54]), and the prevalence for receptor-deficient vs receptor-negative mutation carriers was 1.44% vs 1.12% (OR, 0.49 [95% CI, 0.40-0.60] vs OR, 0.38 [95% CI, 0.29-0.49]), respectively (P for trend <.001 in both comparisons). In a cross-sectional analysis in the Netherlands, the prevalence of type 2 diabetes among patients with familial hypercholesterolemia was significantly lower than among unaffected relatives, with variability by mutation type. If this finding is confirmed in longitudinal analysis, it would raise the possibility of a causal relationship between LDL receptor-mediated transmembrane cholesterol transport and type 2 diabetes.
    JAMA The Journal of the American Medical Association 03/2015; 313(10):1029-1036. DOI:10.1001/jama.2015.1206 · 35.29 Impact Factor
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    ABSTRACT: Background Statins are currently the preferred pharmacological therapy in individuals with familial hypercholesterolemia (FH) with the aim to prevent premature atherosclerosis. In adults, these agents have been proven to be safe and well tolerated; however, non-adherence is a significant clinical issue. Objectives In this study, we evaluated tolerability and adherence to statin therapy in young adult FH patients 10 years after this was initiated in their childhood. Methods A questionnaire including items on medical history, adherence and reasons for discontinuation was sent to 214 young adult FH patients that initiated statin therapy at least 10 years ago. Tolerability was defined as 100 % minus the percentage of patients that discontinued statin therapy due to side effects. Adherence was defined as the extent to which patients took their medication as prescribed by their physician. We labelled patients adherent if they took 80 % or more of their pills in the month preceding our assessment. Results Follow-up was successful in 205 (95.8 %) subjects (age 18–30 years). A history of side effects was reported by 40 (19.5 %) of the patients, and mainly consisted of muscle complaints and gastrointestinal symptoms. Three patients (1.5 %) discontinued statin therapy because of side effects. Rhadbomyolysis or other serious adverse events were not reported. In fact, 169 (82.4 %) of 205 patients remained on statin treatment and 78.7 % (148 out of 188) were adherent. None of the patient characteristics were significantly associated with adherence. Conclusions Individuals with FH who started statin therapy in childhood demonstrated good adherence during ten years of treatment. Furthermore, statin therapy was well tolerated; only a small minority discontinued therapy because of side effects and the side effects that were reported were mild in nature.
    Paediatric Drugs 02/2015; 17(2). DOI:10.1007/s40272-014-0116-y · 1.98 Impact Factor
  • Sigrid W Fouchier · Barbara A Hutten · Joep C Defesche ·
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    ABSTRACT: Autosomal-dominant hypercholesterolaemia (ADH) is a heterogeneous common disorder, and uncovering the molecular determinants that underlie ADH is a major focus of cardiovascular research. However, despite rapid technical advances, efforts to identify novel ADH genes have yet not been very successful and are largely challenged by phenotypic and genetic heterogeneity of this disease. We aimed to investigate the impact of this phenotypic heterogeneity on successfully finding new genes that are involved in ADH. For the ADH phenotype, subjects are considered as affected according to plasma cholesterol levels above the 95th percentile for age and gender. The disease penetrance is generally set at 0.9. These parameters were evaluated in 10 000 carriers of true pathogenic APOB and LDLR mutations and 20 000 relatives negative for the familial mutations. Application of the above parameters in almost a thousand families included in this study would have identified the causal variant in only 38% of all families. An average penetrance of 0.9 or higher, with a cut-point at the 95th percentile, was only observed for LDLR nonsense mutations. For APOB and LDLR missense mutations, a disease penetrance of 0.9 or higher is only expected, when total cholesterol and low-density lipoprotein cholesterol cut-points between the 75th and 90th percentile are used to determine an individual's disease status. Although pathogenic LDLR and APOB mutations do follow Mendelian patterns of inheritance, the extensive variation in genotype and phenotype for well-known ADH-causing mutations emphasises that current criteria and strategies indeed are likely to hamper the identification of novel genes related to ADH. These findings provide a basis for the revision of our assessment on who is affected and who is not and emphasise the essence of pedigree information and mapping data before exome sequencing is applied in order to increase success rates of finding new genes related to ADH. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Journal of Medical Genetics 11/2014; 52(2). DOI:10.1136/jmedgenet-2014-102653 · 6.34 Impact Factor
  • A Kleinjan · B A Hutten · M Di Nisio · H R Büller · P W Kamphuisen ·
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    ABSTRACT: Since 2004, guidelines recommend long-term treatment with low-molecular-weight heparin (LMWH) in patients with cancer and pulmonary embolism (PE). We assessed the proportion of cancer patients with PE actually treated with LMWH and the duration of anticoagulant treatment in the Netherlands. A retrospective cohort study in patients that were hospitalised for PE between 1998-2008. Patients with PE were selected from national hospital discharge records, after linkage to a national pharmacy database. Cancer patients with PE were matched for age, sex and year of diagnosis of PE to subjects with PE without cancer. 600 cancer patients with PE were matched to 1200 patients with PE without cancer. Long-term LMWH was prescribed in 82 (13.7%) of the cancer patients and in eight (0.7%) of the cancer-free patients (p < 0.001); all the other patients received vitamin K antagonists (VKA). From 1998-2008, there was an increase in the use of LMWH in cancer patients: in 2007-2008, LMWH was prescribed in 42 (32%) cases, compared with one (1.7%) of the cancer patients with PE in 1998-1999. Median duration of treatment was 5.8 months (interquartile range 3.1-8.8) in cancer patients, compared with 7.0 months (4.9-11) in patients without cancer (p < 0.001), a difference that persisted after adjustment for mortality. Although the use of LMWH in patients with cancer and PE is increasing, in 2008, patients in the Netherlands are still mostly treated with VKA, and not with LMWH as recommended by guidelines. Cancer patients with PE on average receive shorter treatment than matched patients without cancer.
    The Netherlands Journal of Medicine 11/2014; 72(9):467-73. · 1.97 Impact Factor
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    JAMA The Journal of the American Medical Association 09/2014; 312(10):1055-1057. DOI:10.1001/jama.2014.8892 · 35.29 Impact Factor
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    ABSTRACT: Introduction: Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by severely increased cholesterol levels that lead to an extremely high risk of premature cardiovascular disease (CVD). Aggressive lipid-lowering therapy should be started at an early age with highly potent statins. Rosuvastatin is such a highly efficacious statin with a favorable safety profile that might be advantageous in pediatric HoFH.Areas covered: The authors conducted a PubMed search for rosuvastatin papers and papers on statin use in HoFH published in English. This review describes the pharmacology, safety and efficacy of rosuvastatin and discusses its use in pediatric HoFH.Expert opinion: To date, there is very little evidence on the efficacy and safety of rosuvastatin in pediatric HoFH. Sufficient clinical evidence has proven the lipid-lowering capacity and subsequent CVD prevention of rosuvastatin in hypercholesterolemic adults. Furthermore, clinical studies in children heterozygous familial hypercholesterolemia aged 6 years and older revealed no untoward safety concerns. Rosuvastatin is, therefore, a promising agent in the treatment of pediatric HoFH.
    Expert Opinion on Orphan Drugs 09/2014; 2(12). DOI:10.1517/21678707.2014.958467 · 0.53 Impact Factor

  • Fertility and Sterility 09/2014; 102(3):e82. DOI:10.1016/j.fertnstert.2014.07.279 · 4.59 Impact Factor

Publication Stats

5k Citations
1,079.87 Total Impact Points


  • 2007-2015
    • Netherlands Bioinformatics Centre
      Nymegen, Gelderland, Netherlands
  • 2000-2015
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Clinical Epidemiology and Biostatistics
      • • Department of Vascular Medicine
      • • Academic Medical Center
      Amsterdamo, North Holland, Netherlands
  • 1999-2015
    • University of Amsterdam
      • • Department of Clinical Epidemiology and Biostatistics
      • • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 2010
    • University of Queensland
      • Department of Medicine
      Brisbane, Queensland, Australia
  • 2009
    • AMC Health
      New York, New York, United States
  • 2006
    • Maastricht University
      Maestricht, Limburg, Netherlands
  • 2003
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2001
    • St. Antonius Ziekenhuis
      • Department of Cardiology
      Nieuwegen, Utrecht, Netherlands